Brendan E. Depue

A unified framework for inhibitory control

Inhibiting unwanted thoughts, actions and emotions figures centrally in daily life, and the prefrontal cortex (PFC) is widely viewed as a source of this inhibitory control. We argue that the function of the PFC is best understood in terms of representing and actively maintaining abstract information, such as goals, which produces two types of inhibitory effects on other brain regions. Inhibition of some subcortical regions takes a directed global form, with prefrontal regions providing contextual information relevant to when to inhibit all processing in a region. Inhibition within neocortical (and some subcortical) regions takes an indirect competitive form, with prefrontal regions providing excitation of goal-relevant options. These distinctions are crucial for understanding the mechanisms of inhibition and how they can be impaired or improved.

Cognitive control mechanisms, emotion and memory: A neural perspective with implications for psychopathology

In this paper we provide a focused review of the literature examining neural mechanisms involved in cognitive control over memory processes that can influence, and in turn are influenced by, emotional processes. The review is divided into two parts, the first focusing on working memory and the second on long-term memory. With regard to working memory, we discuss the neural bases of (1) control mechanisms that can select against distracting emotional information, (2) mechanisms that can regulate emotional reactions or responses, (3) how mood state influences cognitive control, and (4) individual differences in control mechanisms. For long-term memory, we briefly review (1) the neural substrates of emotional memory, (2) the cognitive and neural mechanisms that are involved in controlling emotional memories and (3) how these systems are altered in post-traumatic stress disorder. Finally, we consider tentative generalizations that can be drawn from this relatively unexplored conjunction of research endeavors.

Suppression of Emotional and Nonemotional Content in Memory Effects of Repetition on Cognitive Control

Two experiments utilized a think/no-think paradigm to examine whether cognitive control of memories differs depending on whether they contain information with negative or neutral emotional content. During a training phase, participants learned face-word pairs (Experiment 1) or face-picture pairs (Experiment 2). In a subsequent experimental phase, participants were shown faces and told to think of the items paired with some of the faces and to try not to think of the items paired with other faces. Finally, in a test phase, participants were again shown each face and asked to recall the item with which it had been paired previously. Results for both verbal (Experiment 1) and nonverbal (Experiment 2) items indicated that the facilitatory and inhibitory influences of cognitive control were larger for negative than neutral items.

Attentional Control Activation Relates to Working Memory in Attention-Deficit/Hyperactivity Disorder

BACKGROUND Attentional control difficulties in individuals with attention-deficit/hyperactivity disorder (ADHD) might reflect poor working memory (WM) ability, especially because WM ability and attentional control rely on similar brain regions. The current study examined whether WM ability might explain group differences in brain activation between adults with ADHD and normal control subjects during attentional demand. METHODS Participants were 20 adults with ADHD combined subtype with no comorbid psychiatric or learning disorders and 23 control subjects similar in age, IQ, and gender. The WM measures were obtained from the Wechsler Adult Intelligence Scale-III and Wechsler Memory Scale-Revised. Brain activation was assessed with functional magnetic resonance imaging (fMRI) while performing a Color-Word Stroop task. RESULTS Group differences in WM ability explained a portion of the activation in left dorsolateral prefrontal cortex (DLPFC), which has been related to the creation and maintenance of an attentional set for task-relevant information. In addition, greater WM ability predicted increased activation of brain regions related to stimulus-driven attention and response selection processes in the ADHD group but not in the control group. CONCLUSIONS The inability to maintain an appropriate task set in young adults with combined type ADHD, associated with decreased activity in left DLPFC, might in part be due to poor WM ability. Furthermore, in individuals with ADHD, higher WM ability might relate to increased recruitment of stimulus-driven attention and response selection processes, perhaps as a compensatory strategy.

The neural basis of sustained and transient attentional control in young adults with ADHD.

Differences in neural activation during performance on an attentionally demanding Stroop task were examined between 23 young adults with ADHD carefully selected to not be co-morbid for other psychiatric disorders and 23 matched controls. A hybrid blocked/single-trial design allowed for examination of more sustained vs. more transient aspects of attentional control. Our results indicated neural dysregulation across a wide range of brain regions including those involved in overall arousal, top-down attentional control, response selection, and inhibition. Furthermore, this dysregulation was most notable in lateral regions of DLPFC for sustained attentional control and in medial areas for transient aspects of attentional control. Because of the careful selection and matching of our two groups, these results provide strong evidence that the neural systems of attentional control are dysregulated in young adults with ADHD and are similar to dysregulations seen in children and adolescents with ADHD.

Inhibitory Control of Memory Retrieval and Motor Processing Associated with the Right Lateral Prefrontal Cortex: Evidence from Deficits in Individuals with ADHD.

Studies of inhibitory control have focused on inhibition of motor responses. Individuals with ADHD consistently show reductions in inhibitory control and exhibit reduced activity of rLPFC activity compared to controls when performing such tasks. Recently these same brain regions have been implicated in the inhibition of memory retrieval. The degree to which inhibition of motor responses and inhibition of memory retrieval might involve overlapping systems has been relatively unexplored. The current study examined whether inhibitory difficulties in ADHD extend to inhibitory control over memory retrieval. During fMRI 16 individuals with ADHD and 16 controls performed the Think/No-Think (TNT) task. Behaviorally, the Stop Signal Reaction Time task (SSRT) was used to assess inhibitory control over motor responses. To link both of these measures to behavior, the severity of inattentive and hyperactive symptomatology was also assessed. Behaviorally, ADHD individuals had specific difficulty in inhibiting, but not in elaborating/increasing memory retrieval, which was correlated with symptom severity and longer SSRT. Additionally, ADHD individuals showed reduced activity in rLPFC during the TNT, as compared to control individuals. Moreover, unlike controls, in whom the correlation between activity of the rMFG and hippocampus predicts inhibitory success, no such correlation was observed for ADHD individuals. Moreover, decreased activity in rIFG in individuals with ADHD predicted a decrease in the ability to inhibit motor responses. These results suggest that inhibitory functions of rLPFC include control over both memory and motoric processes. They also suggest that inhibitory deficits in individuals with ADHD extend to the memory domain.

Resting-state networks predict individual differences in common and specific aspects of executive function

The goal of the present study was to examine relationships between individual differences in resting state functional connectivity as ascertained by fMRI (rs-fcMRI) and performance on tasks of executive function (EF), broadly defined as the ability to regulate thoughts and actions. Unlike most previous research that focused on the relationship between rs-fcMRI and a single behavioral measure of EF, in the current study we examined the relationship of rs-fcMRI with individual differences in subcomponents of EF. Ninety-one adults completed a resting state fMRI scan and three separate EF tasks outside the magnet: inhibition of prepotent responses, task set shifting, and working memory updating. From these three measures, we derived estimates of common aspects of EF, as well as abilities specific to working memory updating and task shifting. Using Independent Components Analysis (ICA), we identified across the group of participants several networks of regions (Resting State Networks, RSNs) with temporally correlated time courses. We then used dual regression to explore how these RSNs covaried with individual differences in EF. Dual regression revealed that increased higher common EF was associated with connectivity of a) frontal pole with an attentional RSN, and b) Crus I and II of the cerebellum with the right frontoparietal RSN. Moreover, higher shifting-specific abilities were associated with increased connectivity of angular gyrus with a ventral attention RSN. The results of the current study suggest that the organization of the brain at rest may have important implications for individual differences in EF, and that individuals higher in EF may have expanded resting state networks as compared to individuals with lower EF.

Daily Marijuana Use Is Not Associated with Brain Morphometric Measures in Adolescents or Adults

Recent research has suggested that marijuana use is associated with volumetric and shape differences in subcortical structures, including the nucleus accumbens and amygdala, in a dose-dependent fashion. Replication of such results in well controlled studies is essential to clarify the effects of marijuana. To that end, this retrospective study examined brain morphology in a sample of adult daily marijuana users (n = 29) versus nonusers (n = 29) and a sample of adolescent daily users (n = 50) versus nonusers (n = 50). Groups were matched on a critical confounding variable, alcohol use, to a far greater degree than in previously published studies. We acquired high-resolution MRI scans, and investigated group differences in gray matter using voxel-based morphometry, surface-based morphometry, and shape analysis in structures suggested to be associated with marijuana use, as follows: the nucleus accumbens, amygdala, hippocampus, and cerebellum. No statistically significant differences were found between daily users and nonusers on volume or shape in the regions of interest. Effect sizes suggest that the failure to find differences was not due to a lack of statistical power, but rather was due to the lack of even a modest effect. In sum, the results indicate that, when carefully controlling for alcohol use, gender, age, and other variables, there is no association between marijuana use and standard volumetric or shape measurements of subcortical structures.

Behavioral performance predicts grey matter reductions in the right inferior frontal gyrus in young adults with combined type ADHD

Optimized voxel-based morphometry (VBM) was used in the present study to investigate morphometric differences between young adults with combined type Attention Deficit/Hyperactivity Disorder (ADHD) and a well-matched control group. Investigations examined differences on a between-group whole brain level, as well as how individual differences in behavioral performance predicted grey matter differences. Although a whole brain analysis revealed no significant differences between ADHD and control individuals, ADHD but not control individuals exhibited reduced grey matter volume in the right inferior frontal gyrus (rIFG), predicted by poorer behavioral performance on all three measures. A subsequent region-of-interest approach revealed lower grey matter volume in the rIFG in ADHD compared to control individuals. These results suggest that young adults with ADHD show morphometric differences in inferior prefrontal regions, as compared to controls. These morphometric differences are related to disruptions in performance on behavioral tasks that frequently have been reported to be affected in individuals with ADHD.

A neuroanatomical model of prefrontal inhibitory modulation of memory retrieval

Memory of past experience is essential for guiding goal-related behavior. Being able to control accessibility of memory through modulation of retrieval enables humans to flexibly adapt to their environment. Understanding the specific neural pathways of how this control is achieved has largely eluded cognitive neuroscience. Accordingly, in the current paper I review literature that examines the overt control over retrieval in order to reduce accessibility. I first introduce three hypotheses of inhibition of retrieval. These hypotheses involve: (i) attending to other stimuli as a form of diversionary attention, (ii) inhibiting the specific individual neural representation of the memory, and (iii) inhibiting the hippocampus and retrieval process more generally to prevent reactivation of the representation. I then analyze literature taken from the White Bear Suppression, Directed Forgetting and Think/No-Think tasks to provide evidence for these hypotheses. Finally, a neuroanatomical model is developed to indicate three pathways from PFC to the hippocampal complex that support inhibition of memory retrieval. Describing these neural pathways increases our understanding of control over memory in general.